Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization
Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization
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DOI：
10.1016/s0960-9822(97)70090-3
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发表时间：
1997-03-01
期刊：
影响因子：
9.2
通讯作者：
Frohman, MA
中科院分区：
文献类型：
--
作者：
Colley, WC;Sung, TC;Frohman, MA
背景资料：磷脂酶D（PLD）的激活是受体介导的信号转导应答和调节分泌的重要但知之甚少的组分。我们最近报道了编码PLD 1的人类基因的克隆;该酶具有低的基础活性，并且被蛋白激酶C和小GTP结合蛋白、ADP-核糖基化因子（ARF）、Rho、Rac和Cdc 42激活。然而，生物化学和细胞生物学研究表明，在细胞中存在额外的和独特的PLD活性，因此进行了与PLD 1相关的新的哺乳动物基因的搜索。结果：我们已经克隆了第二个PLD家族成员的基因，并表征了蛋白产物，其似乎与PLD 1不同地调节：PLD 2是组成型活性的，并且可以通过抑制在体内调节。出乎意料的是，PLD 2主要定位于质膜，与仅定位于核周围区域的PLD 1相反（内质网、高尔基体和晚期核内体），其中PLD活性已显示促进ARF介导的包被囊泡形成，PLD 2引起皮质重组并在血清刺激的细胞中经历再分布，提示它可能在信号诱导的细胞骨架调节和/或内吞作用中起作用。PLD 2是一种新发现的哺乳动物PLD亚型，具有新的调节特性，我们的研究结果表明，PLD 2的分泌调节和形态重组，PLD的两种最常被提出的生物学作用可能分别受到PLD 1和PLD 2的影响。
Background: Activation of phospholipase D (PLD) is an important but poorly understood component of receptor-mediated signal transduction responses and regulated secretion, We recently reported the cloning of the human gene encoding PLD1;this enzyme has low basal activity and is activated by protein kinase C and the small GTP-binding proteins, ADP-ribosylation factor (ARF), Rho, Rac and Cdc42. Biochemical and cell biological studies suggest, however, that additional and distinct PLD activities exist in cells, so a search was carried out for novel mammalian genes related to PLD1.Results: We have cloned the gene for a second PLD family member and characterized the protein product, which appears to be regulated differently from PLD1:PLD2 is constitutively active and may be modulated in vivo by inhibition, Unexpectedly, PLD2 localizes primarily to the plasma membrane, in contrast to PLD1 which localizes solely to peri-nuclear regions (the endoplasmic reticulum, Golgi apparatus and late endosomes), where PLD activity has been shown to promote ARF-mediated coated-vesicle formation, PLD2 provokes cortical reorganization and undergoes redistribution in serum-stimulated cells, suggesting that it may have a role in signal-induced cytoskeletal regulation and/or endocytosis.Conclusions: PLD2 is a newly identified mammalian PLD isoform with novel regulatory properties, Our findings suggest that regulated secretion and morphological reorganization, the two most frequently proposed biological roles for PLD, are likely to be effected separately by PLD1 and PLD2.